Abstract

The glutamatergic system plays a role in certain common behavioral manifestations of posttraumatic stress disorder (PTSD), e.g. mechanisms of fear learning and anxious arousal. We propose to evaluate the efficacy of the mGlu2/3 receptor agonist pomaglumetad methionil in treating PTSD in a randomized, double-blind, placebo-controlled, phase II clinical trial. Key endpoints of this trial include structured diagnostic and self- report measures of PTSD and related symptomatology, as well as objective biomarkers of fear acquisition and expression. Evaluation of the differential efficacy of the mGlu2/3 agonist pomaglumetad methionil on symptom clusters that comprise the theory-driven and empirically-supported five-factor phenotypic model of PTSD symptoms will provide greater specificity regarding how this drug differentially modulates unique dimensions of the PTSD phenotype. Given the inhibitory effects of mGlu2/3 receptor agonists on stress-induced NE secretion, we predict that pomaglumetad methionil will have the most pronounced effect in mitigating anxious arousal symptoms.!

Public Health Relevance

This application aims to determine the role of the mGlu2/3 agonist pomaglumetad methionil in the treatment of posttraumatic stress disorder (PTSD). We propose to recruit patients with PTSD, and will conduct a placebo- controlled, double-blind, randomized clinical trial. Key endpoints of this trial include structured diagnostic and self-repor measures of PTSD and related symptomatology, as well as objective biomarkers of fear acquisition and expression.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Planning Grant (R34)
Project #
1R34MH102871-01
Application #
8650643
Study Section
Interventions Committee for Adult Disorders (ITVA)
Program Officer
Borja, Susan
Project Start
2014-07-09
Project End
2017-06-30
Budget Start
2014-07-09
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
$332,384
Indirect Cost
$131,308

  Institution

Name
New York University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016

  Publications

Neumeister, Alexander; Seidel, Jordan; Ragen, Benjamin J et al. (2015) Translational evidence for a role of endocannabinoids in the etiology and treatment of posttraumatic stress disorder. Psychoneuroendocrinology 51:577-84
Ragen, Benjamin J; Seidel, Jordan; Chollak, Christine et al. (2015) Investigational drugs under development for the treatment of PTSD. Expert Opin Investig Drugs 24:659-72
Pietrzak, Robert H; Huang, Yiyun; Corsi-Travali, Stefani et al. (2014) Cannabinoid type 1 receptor availability in the amygdala mediates threat processing in trauma survivors. Neuropsychopharmacology 39:2519-28